tbuckley/cabot-search huggingface dataset:
COVID-19 Vaccination Recommendations and Practices for Women of Reproductive Age by Health Care Providers — Fall DocStyles Survey, United States, 2022
Authors: Mehreen Meghani, Beatriz Salvesen Von Essen, Lauren B. Zapata, Kara Polen, Romeo R. Galang, Hilda Razzaghi, Dana Meaney-Delman, Grayson Waits, Sascha Ellington
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Pregnant and postpartum women are at increased risk for severe illness from COVID-19 compared with nonpregnant women of reproductive age.COVID-19 vaccination is recommended for all persons ≥6 months of age.Health care providers (HCPs) have a unique opportunity to counsel women of reproductive age, including pregnant and postpartum patients, about the importance of receiving COVID-19, influenza, and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines.Data from the Fall 2022 DocStyles survey were analyzed to examine the prevalence of COVID-19 vaccination attitudes and practices among HCPs caring for women of reproductive age, and to determine whether providers recommended and offered or administered COVID-19 vaccines to women of reproductive age, including their pregnant patients.Overall, 82.9% of providers reported recommending COVID-19 vaccination to women of reproductive age, and 54.7% offered or administered the vaccine in their practice.Among HCPs who cared for pregnant patients, obstetrician-gynecologists were more likely to recommend COVID-19 vaccination to pregnant patients (94.2%) than were family practitioners or internists (82.1%) (adjusted prevalence ratio [aPR] = 1.1).HCPs were more likely to offer or administer COVID-19 vaccination on-site to pregnant patients if they also offered or administered influenza (aPR = 5.5) and Tdap vaccines (aPR = 2.3).Encouraging HCPs to recommend, offer, and administer the COVID-19 vaccines along with influenza or Tdap vaccines might help reinforce vaccine confidence and increase coverage among women of reproductive age, including pregnant women.* https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html
Inequities in COVID-19 Vaccination Coverage Among Pregnant Persons, by Disaggregated Race and Ethnicity — Massachusetts, May 2021–October 2022
Authors: Hanna M. Shephard, Susan E. Manning, Eirini Nestoridi, Anne Marie Darling, Catherine M. Brown, Megan Hatch, Kathryn Ahnger-Pier, Sharon Pagnano, Darien Mather, Mahsa M. Yazdy
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

National estimates suggest that COVID-19 vaccination coverage among pregnant persons is lower among those identifying as Hispanic or Latino (Hispanic) and non-Hispanic Black or African American. When examining COVID-19 vaccination coverage during pregnancy by race and ethnicity, however, data are typically limited to large, aggregate categories that might obscure within-group inequities. To address this, Massachusetts examined COVID-19 vaccination coverage among pregnant persons by combinations of 12 racial and 34 ethnic groupings. Among 102,275 persons with a live birth in Massachusetts during May 1, 2021-October 31, 2022, receipt of ≥1 dose of a COVID-19 vaccine before or during pregnancy was 41.6% overall and was highest among persons who identified as Asian (55.0%) and lowest among those who identified as Hispanic (26.7%). However, within all broad racial and ethnic groupings, disparities in COVID-19 vaccination coverage were identified when the data were disaggregated into more granular categories; for example, COVID-19 vaccination coverage ranged from 10.8%-61.1% among pregnant persons who identified as Hispanic. Disaggregated analyses reveal diverse experiences within broad racial and ethnic groupings. This information can be used to guide outreach to pregnant persons in communities with lower rates of COVID-19 vaccination coverage during pregnancy.
Deep representation learning identifies associations between physical activity and sleep patterns during pregnancy and prematurity
Authors: Neal G. Ravindra, Camilo Espinosa, Eloïse Berson, Thanaphong Phongpreecha, Peinan Zhao, Martin Becker, Alan L. Chang, Sayane Shome, Ivana Marić, Davide De Francesco, Samson Mataraso, Geetha Saarunya, Melan Thuraiappah, Lei Xue, Brice Gaudillière, Martin S. Angst, Gary M. Shaw, Erik D. Herzog, David K. Stevenson, Sarah K. England, Nima Aghaeepour
Journal: npj Digital Medicine (2023)

Abstract Preterm birth (PTB) is the leading cause of infant mortality globally. Research has focused on developing predictive models for PTB without prioritizing cost-effective interventions. Physical activity and sleep present unique opportunities for interventions in low- and middle-income populations (LMICs). However, objective measurement of physical activity and sleep remains challenging and self-reported metrics suffer from low-resolution and accuracy. In this study, we use physical activity data collected using a wearable device comprising over 181,944 h of data across N = 1083 patients. Using a new state-of-the art deep learning time-series classification architecture, we develop a ‘clock’ of healthy dynamics during pregnancy by using gestational age (GA) as a surrogate for progression of pregnancy. We also develop novel interpretability algorithms that integrate unsupervised clustering, model error analysis, feature attribution, and automated actigraphy analysis, allowing for model interpretation with respect to sleep, activity, and clinical variables. Our model performs significantly better than 7 other machine learning and AI methods for modeling the progression of pregnancy. We found that deviations from a normal ‘clock’ of physical activity and sleep changes during pregnancy are strongly associated with pregnancy outcomes. When our model underestimates GA, there are 0.52 fewer preterm births than expected ( P = 1.01e − 67, permutation test) and when our model overestimates GA, there are 1.44 times ( P = 2.82e − 39, permutation test) more preterm births than expected. Model error is negatively correlated with interdaily stability ( P = 0.043, Spearman’s), indicating that our model assigns a more advanced GA when an individual’s daily rhythms are less precise. Supporting this, our model attributes higher importance to sleep periods in predicting higher-than-actual GA, relative to lower-than-actual GA ( P = 1.01e − 21, Mann-Whitney U). Combining prediction and interpretability allows us to signal when activity behaviors alter the likelihood of preterm birth and advocates for the development of clinical decision support through passive monitoring and exercise habit and sleep recommendations, which can be easily implemented in LMICs.
Efficacy of cell-free DNA methylation-based blood test for colorectal cancer screening in high-risk population: a prospective cohort study
Authors: Fuqiang Zhao, Ping Bai, Jianfeng Xu, Zitong Li, Shan Muhammad, Diange Li, Zeyue Zhang, Yibo Gao, Qian Liu
Journal: Molecular Cancer (2023)

Although colonoscopy is the standard screening test for colorectal cancer (CRC), its use is limited by a poor compliance rate, the need for extensive bowel preparation, and the risk of complications. As an alternative, an FDA-approved stool-based DNA test, Cologuard, has demonstrated satisfactory detection performance for CRC, but its compliance rate remains suboptimal, primarily attributable to individuals' reluctance to provide stool samples.We developed a noninvasive blood-based CRC test, ColonSecure, based on cell-free DNA containing cancer-specific CpG island methylation patterns. We initially screened publicly available datasets for differentially methylated CpG sites in CRC with prediction potential. Subsequently, we performed two sequential bisulfite-free methylation sequencing on blood samples obtained from CRC patients and non-cancer controls. Through rigorous evaluation of each marker and machine learning-assisted feature selection, we identified 149 hypermethylated markers from over 193,000 CpG sites. These markers were then utilized to construct the ColonSecure model, enabling accurate CRC detection.We validated the efficacy of our cell-free DNA methylation-based blood test for CRC screening with 3493 high-risk individuals identified from 114,136 urban residents. The ColonSecure test identified 89 out of 103 CRC patients diagnosed by the follow-up colonoscopy, outperforming CEA, CRP, and CA19-9 (with a sensitivity of 86.4% compared to 45.6%, 39.8%, and 25.2% for CEA, CRP, and CA19-9 respectively; an AUROC of 0.956 compared to an AUROC of < 0.77 for other methods).Our observations emphasize the potential of our multiple cfDNA methylation marker-based test for CRC screening in high-risk populations.
Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial
Authors: Jerry Vockley, Neal Sondheimer, Marja Puurunen, George A. Diaz, Ilona Ginevic, Dorothy K. Grange, Cary Harding, Hope Northrup, John A. Phillips, Shawn Searle, Janet A. Thomas, Roberto Zori, William S. Denney, Sharon L. Ernst, Kristina Humphreys, Nicole McWhorter, Caroline Kurtz, Aoife M. Brennan
Journal: Nature Metabolism (2023)
Functional screening and rational design of compounds targeting GPR132 to treat diabetes
Authors: Jia-Le Wang, Xiao-Dong Dou, Jie Cheng, Ming-Xin Gao, Guo-Feng Xu, Wei Ding, Jin-Hui Ding, Yu Li, Si-Han Wang, Zhao-Wei Ji, Xin-Yi Zhao, Tong-Yu Huo, Cai-Fang Zhang, Ya-Meng Liu, Xue-Ying Sha, Jia-Rui Gao, Wen-Hui Zhang, Yong Hao, Cheng Zhang, Jin-Peng Sun, Ning Jiao, Xiao Yu
Journal: Nature Metabolism (2023)
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
Authors: Maryam Kavousi, Maxime M. Bos, Hanna J. Barnes, Christian L. Lino Cardenas, Doris Wong, Haojie Lu, Chani J. Hodonsky, Lennart P. L. Landsmeer, Adam W. Turner, Minjung Kho, Natalie R. Hasbani, Paul S. de Vries, Donald W. Bowden, Sandesh Chopade, Joris Deelen, Ernest Diez Benavente, Xiuqing Guo, Edith Hofer, Shih-Jen Hwang, Sharon M. Lutz, Leo-Pekka Lyytikäinen, Lotte Slenders, Albert V. Smith, Maggie A. Stanislawski, Jessica van Setten, Quenna Wong, Lisa R. Yanek, Diane M. Becker, Marian Beekman, Matthew J. Budoff, Mary F. Feitosa, Chris Finan, Austin T. Hilliard, Sharon L. R. Kardia, Jason C. Kovacic, Brian G. Kral, Carl D. Langefeld, Lenore J. Launer, Shaista Malik, Firdaus A. A. Mohamed Hoesein, Michal Mokry, Reinhold Schmidt, Jennifer A. Smith, Kent D. Taylor, James G. Terry, Jeroen van der Grond, Joyce van Meurs, Rozemarijn Vliegenthart, Jianzhao Xu, Kendra A. Young, Nuno R. Zilhão, Robert Zweiker, Themistocles L. Assimes, Lewis C. Becker, Daniel Bos, J. Jeffrey Carr, L. Adrienne Cupples, Dominique P. v. de Kleijn, Menno de Winther, Hester M. den Ruijter, Myriam Fornage, Barry I. Freedman, Vilmundur Gudnason, Aroon D. Hingorani, John E. Hokanson, M. Arfan Ikram, Ivana Išgum, David R. Jacobs, Mika Kähönen, Leslie A. Lange, Terho Lehtimäki, Gerard Pasterkamp, Olli T. Raitakari, Helena Schmidt, P. Eline Slagboom, André G. Uitterlinden, Meike W. Vernooij, Joshua C. Bis, Nora Franceschini, Bruce M. Psaty, Wendy S. Post, Jerome I. Rotter, Johan L. M. Björkegren, Christopher J. O’Donnell, Lawrence F. Bielak, Patricia A. Peyser, Rajeev Malhotra, Sander W. van der Laan, Clint L. Miller
Journal: Nature Genetics (2023)
Multitissue H3K27ac profiling of GTEx samples links epigenomic variation to disease
Authors: Lei Hou, Xushen Xiong, Yongjin Park, Carles Boix, Benjamin James, Na Sun, Liang He, Aman Patel, Zhizhuo Zhang, Benoit Molinie, Nicholas Van Wittenberghe, Scott Steelman, Chad Nusbaum, François Aguet, Kristin G. Ardlie, Manolis Kellis
Journal: Nature Genetics (2023)

Abstract Genetic variants associated with complex traits are primarily noncoding, and their effects on gene-regulatory activity remain largely uncharacterized. To address this, we profile epigenomic variation of histone mark H3K27ac across 387 brain, heart, muscle and lung samples from Genotype-Tissue Expression (GTEx). We annotate 282 k active regulatory elements (AREs) with tissue-specific activity patterns. We identify 2,436 sex-biased AREs and 5,397 genetically influenced AREs associated with 130 k genetic variants (haQTLs) across tissues. We integrate genetic and epigenomic variation to provide mechanistic insights for disease-associated loci from 55 genome-wide association studies (GWAS), by revealing candidate tissues of action, driver SNPs and impacted AREs. Lastly, we build ARE–gene linking scores based on genetics (gLink scores) and demonstrate their unique ability to prioritize SNP–ARE–gene circuits. Overall, our epigenomic datasets, computational integration and mechanistic predictions provide valuable resources and important insights for understanding the molecular basis of human diseases/traits such as schizophrenia.
Immunosuppressive CD29<sup>+</sup>Treg accumulation in the liver in mice on checkpoint inhibitor therapy
Authors: Benjamin L Green, Yuta Myojin, Chi Ma, Benjamin Ruf, Lichun Ma, Qianfei Zhang, Umberto Rosato, Jonathan Qi, Mahler Revsine, Simon Wabitsch, Kylynda Bauer, Mohamed-Reda Benmebarek, Justin McCallen, Amran Nur, Xin Wang, Vivek Sehra, Revant Gupta, Manfred Claassen, Xin Wei Wang, Firouzeh Korangy, Tim F Greten
Journal: Gut (2023)

Objective Liver metastases are often resistant to immune checkpoint inhibitor therapy (ICI) and portend a worse prognosis compared with metastases to other locations. Regulatory T cells (Tregs) are one of several immunosuppressive cells implicated in ICI resistance of liver tumours, but the role played by Tregs residing within the liver surrounding a tumour is unknown. Design Flow cytometry and single-cell RNA sequencing were used to characterise hepatic Tregs before and after ICI therapy. Results We found that the murine liver houses a Treg population that, unlike those found in other organs, is both highly proliferative and apoptotic at baseline. On administration of αPD-1, αPD-L1 or αCTLA4, the liver Treg population doubled regardless of the presence of an intrahepatic tumour. Remarkably, this change was not due to the preferential expansion of the subpopulation of Tregs that express PD-1. Instead, a subpopulation of CD29 + ( Itgb1 , integrin β1) Tregs, that were highly proliferative at baseline, doubled its size in response to αPD-1. Partial and full depletion of Tregs identified CD29 + Tregs as the prominent niche-filling subpopulation in the liver, and CD29 + Tregs demonstrated enhanced suppression in vitro when derived from the liver but not the spleen. We identified IL2 as a critical modulator of both CD29 + and CD29 − hepatic Tregs, but expansion of the liver Treg population with αPD-1 driven by CD29 + Tregs was in part IL2-independent. Conclusion We propose that CD29 + Tregs constitute a unique subpopulation of hepatic Tregs that are primed to respond to ICI agents and mediate resistance.
<i>Lactobacillus gallinarum</i>-derived metabolites boost anti-PD1 efficacy in colorectal cancer by inhibiting regulatory T cells through modulating IDO1/Kyn/AHR axis
Authors: Winnie Fong, Qing Li, Fenfen Ji, Wei Liang, Harry Cheuk Hay Lau, Xing Kang, Weixin Liu, Kenneth Kin-Wah To, Zhong Zuo, Xiaoxing Li, Xiang Zhang, Joseph JY Sung, Jun Yu
Journal: Gut (2023)

Objective Gut microbiota is a key player in dictating immunotherapy response. We aimed to explore the immunomodulatory effect of probiotic Lactobacillus gallinarum and its role in improving anti-programmed cell death protein 1 (PD1) efficacy against colorectal cancer (CRC). Design The effects of L. gallinarum in anti-PD1 response were assessed in syngeneic mouse models and azoxymethane/dextran sulfate sodium-induced CRC model. The change of immune landscape was identified by multicolour flow cytometry and validated by immunohistochemistry staining and in vitro functional assays. Liquid chromatography-mass spectrometry was performed to identify the functional metabolites. Results L. gallinarum significantly improved anti-PD1 efficacy in two syngeneic mouse models with different microsatellite instability (MSI) statuses (MSI-high for MC38, MSI-low for CT26). Such effect was confirmed in CRC tumourigenesis model. L. gallinarum synergised with anti-PD1 therapy by reducing Foxp3 + CD25 + regulatory T cell (Treg) intratumoural infiltration, and enhancing effector function of CD8 + T cells. L. gallinarum -derived indole-3-carboxylic acid (ICA) was identified as the functional metabolite. Mechanistically, ICA inhibited indoleamine 2,3-dioxygenase (IDO1) expression, therefore suppressing kynurenine (Kyn) production in tumours. ICA also competed with Kyn for binding site on aryl hydrocarbon receptor (AHR) and antagonised Kyn binding on CD4 + T cells, thereby inhibiting Treg differentiation in vitro. ICA phenocopied L. gallinarum effect and significantly improved anti-PD1 efficacy in vivo, which could be reversed by Kyn supplementation. Conclusion L. gallinarum -derived ICA improved anti-PD1 efficacy in CRC through suppressing CD4+Treg differentiation and enhancing CD8+T cell function by modulating the IDO1/Kyn/AHR axis. L. gallinarum is a potential adjuvant to augment anti-PD1 efficacy against CRC.
British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma
Authors: Simon M Rushbrook, Timothy James Kendall, Yoh Zen, Raneem Albazaz, Prakash Manoharan, Stephen P Pereira, Richard Sturgess, Brian R Davidson, Hassan Z Malik, Derek Manas, Nigel Heaton, K Raj Prasad, John Bridgewater, Juan W Valle, Rebecca Goody, Maria Hawkins, Wendy Prentice, Helen Morement, Martine Walmsley, Shahid A Khan
Journal: Gut (2023)

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations.
Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo
Authors: Emma Guttman-Yassky, Ester Del Duca, Joel Correa Da Rosa, Jonathan Bar, Khaled Ezzedine, Zhan Ye, Wen He, Craig Hyde, Mina Hassan-Zahraee, Yuji Yamaguchi, Elena Peeva
Journal: Journal of Allergy and Clinical Immunology (2023)

Background Vitiligo is an autoimmune depigmenting disorder with no effective and safe treatments. Its pathogenesis is not fully elucidated. Objective This substudy of a randomized, double-blind, placebo-controlled phase 2b trial (NCT03715829) evaluated effects of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on skin and blood biomarkers in participants with non-segmental vitiligo (NSV). Methods 65 adults with NSV participated in the substudy and received daily treatment for 24 weeks with placebo (n=14) or ritlecitinib with or without a 4-week loading dose: 200 (loading dose)/50 mg (n=13), 100/50 mg (n=12), 50 mg (n=11), 30 mg (n=8), or 10 mg (n=6). Skin (lesional and nonlesional) biopsies were taken at baseline, 4, and 24 weeks. Changes from baseline to weeks 4 and 24 in skin and blood molecular/cellular biomarkers were evaluated by RNA-seq/RT-qPCR/proteomics/flow cytometry. Results Ritlecitinib-treated groups showed downregulation of immune biomarkers and upregulation of melanocyte-related markers at weeks 4 and 24 compared with baseline and/or placebo. Significant reductions were seen in CD3+/CD8+ T-cell infiltrates, with significant increases in melanocyte markers (tyrosinase; Melan-A) in NSV lesions in the 50-mg ritlecitinib groups (both P<0.05). There was significant, dose-dependent downregulation in T-cell activation/NK/cytotoxic/regulatory markers in lesional skin (IL-2/IL2-RA/IL-15/CCR7/CD5/ CRTAM/NCR1/XCL1/KIR3DL1/FASLG/KLRD; P<0.05). Th1 and Th2 markers were also downregulated in lesional skin and blood in a dose-dependent manner (P<0.05). Changes in immune biomarkers correlated with clinical response. Conclusion Ritlecitinib significantly downregulated pro-inflammatory biomarkers and increased melanocyte products in skin and blood of participants with NSV, suggesting its potential in treatment. Ritlecitinib-mediated changes positively correlated with clinical response.
SARS-CoV-2 infection following booster vaccination: Illness and symptom profile in a prospective, observational community-based case-control study
Authors: Michela Antonelli, Rose S. Penfold, Liane Dos Santos Canas, Carole Sudre, Khaled Rjoob, Ben Murray, Erika Molteni, Eric Kerfoot, Nathan Cheetham, Juan Capdevila Pujol, Lorenzo Polidori, Anna May, Jonathan Wolf, Marc Modat, Tim Spector, Alexander Hammers, Sebastien Ourselin, Claire Steves
Journal: Journal of Infection (2023)

Booster COVID-19 vaccines have shown efficacy in clinical trials and effectiveness in real-world data against symptomatic and severe illness. However, some people still become infected with SARS-CoV-2 following a third (booster) vaccination. This study describes the characteristics of SARS-CoV-2 illness following a third vaccination and assesses the risk of progression to symptomatic disease in SARS-CoV-2 infected individuals with time since vaccination.
Commoning genomic solidarity to improve global health equality
Authors: Joy Y. Zhang
Journal: Cell Genomics (2023)

This article underlines two key asynchronies between prevailing governing logic and expanding practices in somatic human genome editing that are hindering an effective and orderly translation of the new technology into public good. The first is a "genomic sovereignty" framing adopted by a number of non-Western countries that may exacerbate data biases in global research and that directs policy attention away from the necessary structural changes required to achieve non-discriminatory and equitable genomic healthcare. The other is a global deficiency in attending to "science at large": the challenge of regulating new assemblages of societal interests that advocate controversial or experimental research, often outside of conventional institutions and aided by "policy shopping." Both issues point to the fact that genomic research does not represent a well-defined scientific commons but rather a domain that requires active "commoning," with the aim of fostering genomic solidarity that coordinates responsible research within and across national boundaries.